• Gene id: 9451

Gene Summary

• Gene Symbol: EIF2AK3   Gene   UCSC   Ensembl
• Aliases: PEK, PERK, WRS
• Gene name: eukaryotic translation initiation factor 2 alpha kinase 3
• Alternate names: eukaryotic translation initiation factor 2-alpha kinase 3, PRKR-like endoplasmic reticulum kinase, pancreatic EIF2-alpha kinase, truncated eukaryotic translation initiation factor 2 alpha kinase 3,
• Gene location: 2p11.2 (88627463: 88556739)     Exons: 19     NC_000002.12
• Gene summary(Entrez): The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protei
• OMIM: 605662

Protein Summary

• Protein general information: Q9NZJ5  
  • Name: Eukaryotic translation initiation factor 2 alpha kinase 3 (EC 2.7.11.1) (PRKR like endoplasmic reticulum kinase) (Pancreatic eIF2 alpha kinase) (HsPEK)
  • Length: 1116  
  • Mass: 125216
  • Tissue specificity: Ubiquitous. A high level expression is seen in secretory tissues.
• Sequence:

  MERAISPGLLVRALLLLLLLLGLAARTVAAGRARGLPAPTAEAAFGLGAAAAPTSATRVPAAGAVAAAEVTVEDA
  EALPAAAGEQEPRGPEPDDETELRPRGRSLVIISTLDGRIAALDPENHGKKQWDLDVGSGSLVSSSLSKPEVFGN
  KMIIPSLDGALFQWDQDRESMETVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKVRYICSALGCRQWD
  SDEMEQEEDILLLQRTQKTVRAVGPRSGNEKWNFSVGHFELRYIPDMETRAGFIESTFKPNENTEESKIISDVEE
  QEAAIMDIVIKVSVADWKVMAFSKKGGHLEWEYQFCTPIASAWLLKDGKVIPISLFDDTSYTSNDDVLEDEEDIV
  EAARGATENSVYLGMYRGQLYLQSSVRISEKFPSSPKALESVTNENAIIPLPTIKWKPLIHSPSRTPVLVGSDEF
  DKCLSNDKFSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDNPHYNKNIRKKDPVLLLHWWKEI
  VATILFCIIATTFIVRRLFHPHPHRQRKESETQCQTENKYDSVSGEANDSSWNDIKNSGYISRYLTDFEPIQCLG
  RGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLEAPPEKWQEKMDEIWL
  KDESTDWPLSSPSPMDAPSVKIRRMDPFATKEHIEIIAPSPQRSRSFSVGISCDQTSSSESQFSPLEFSGMDHED
  ISESVDAAYNLQDSCLTDCDVEDGTMDGNDEGHSFELCPSEASPYVRSRERTSSSIVFEDSGCDNASSKEEPKTN
  RLHIGNHCANKLTAFKPTSSKSSSEATLSISPPRPTTLSLDLTKNTTEKLQPSSPKVYLYIQMQLCRKENLKDWM
  NGRCTIEERERSVCLHIFLQIAEAVEFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPM
  PAYARHTGQVGTKLYMSPEQIHGNSYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPCE
  YVMVQDMLSPSPMERPEAINIIENAVFEDLDFPGKTVLRQRSRSLSSSGTKHSRQSNNSHSPLPSN

• Structural information:
  • Protein Domains: (593..107-)
    (/note="Protein-kinase)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"-)
  • Interpro: IPR011009  IPR000719  IPR017441  IPR011047  IPR008271   IPR015943  
  • Prosite: PS00107 PS50011 PS00108
  • PDB: 4G31 4G34 4M7I 4X7H 4X7J 4X7K 4X7L 4X7N 4X7O 4YZS 5SV7
  • PDBsum: 4G31 4G34 4M7I 4X7H 4X7J 4X7K 4X7L 4X7N 4X7O 4YZS 5SV7
  • STRING: ENSP00000307235
• Other Databases: GeneCards:  EIF2AK3  Malacards:  EIF2AK3

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0030176	integral component of endoplasmic reticulum membrane	NAS	cellular component
GO:0030176	integral component of endoplasmic reticulum membrane	NAS	cellular component
GO:0005515	protein binding	IPI	molecular function
GO:0010998	regulation of translational initiation by eIF2 alpha phosphorylation	ISS	biological process
GO:0042149	cellular response to glucose starvation	IMP	biological process
GO:0010628	positive regulation of gene expression	IMP	biological process
GO:0018105	peptidyl-serine phosphorylation	ISS	biological process
GO:0036492	eiF2alpha phosphorylation in response to endoplasmic reticulum stress	TAS	biological process
GO:0001525	angiogenesis	IMP	biological process
GO:1900182	positive regulation of protein localization to nucleus	ISS	biological process
GO:0010575	positive regulation of vascular endothelial growth factor production	IMP	biological process
GO:1902235	regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IMP	biological process
GO:0045943	positive regulation of transcription by RNA polymerase I	IMP	biological process
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IBA	molecular function
GO:0004672	protein kinase activity	IBA	molecular function
GO:0030968	endoplasmic reticulum unfolded protein response	IDA	biological process
GO:0034198	cellular response to amino acid starvation	IMP	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0070417	cellular response to cold	IMP	biological process
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IMP	molecular function
GO:0036492	eiF2alpha phosphorylation in response to endoplasmic reticulum stress	IMP	biological process
GO:0060734	regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	ISS	biological process
GO:0019903	protein phosphatase binding	IPI	molecular function
GO:0004672	protein kinase activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0006468	protein phosphorylation	IEA	biological process
GO:0006986	response to unfolded protein	IEA	biological process
GO:0006417	regulation of translation	IEA	biological process
GO:0016301	kinase activity	IEA	molecular function
GO:0016740	transferase activity	IEA	molecular function
GO:0005783	endoplasmic reticulum	IEA	cellular component
GO:0004674	protein serine/threonine kinase activity	IEA	molecular function
GO:0005524	ATP binding	IEA	molecular function
GO:0016020	membrane	IEA	cellular component
GO:0016310	phosphorylation	IEA	biological process
GO:0000166	nucleotide binding	IEA	molecular function
GO:0016021	integral component of membrane	IEA	cellular component
GO:0004672	protein kinase activity	TAS	molecular function
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0005789	endoplasmic reticulum membrane	TAS	cellular component
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0042802	identical protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0046777	protein autophosphorylation	IEA	biological process
GO:0048471	perinuclear region of cytoplasm	IEA	cellular component
GO:0004674	protein serine/threonine kinase activity	IEA	molecular function
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IEA	molecular function
GO:0006468	protein phosphorylation	IEA	biological process
GO:0032055	negative regulation of translation in response to stress	IEA	biological process
GO:0051879	Hsp90 protein binding	IEA	molecular function
GO:1990737	response to manganese-induced endoplasmic reticulum stress	IEA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	TAS	biological process
GO:0032057	negative regulation of translational initiation in response to stress	TAS	biological process
GO:0034976	response to endoplasmic reticulum stress	IMP	biological process
GO:0005789	endoplasmic reticulum membrane	IEA	cellular component
GO:0046777	protein autophosphorylation	IDA	biological process
GO:0046777	protein autophosphorylation	IDA	biological process
GO:0006983	ER overload response	IDA	biological process
GO:0006983	ER overload response	IDA	biological process
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IDA	molecular function
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IDA	molecular function
GO:0030968	endoplasmic reticulum unfolded protein response	IDA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	IDA	biological process
GO:0005783	endoplasmic reticulum	IC	cellular component
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IDA	molecular function
GO:0019899	enzyme binding	IPI	molecular function
GO:0016020	membrane	HDA	cellular component
GO:0031018	endocrine pancreas development	IMP	biological process
GO:0019722	calcium-mediated signaling	ISS	biological process
GO:0007029	endoplasmic reticulum organization	ISS	biological process
GO:0006468	protein phosphorylation	ISS	biological process
GO:0005737	cytoplasm	ISS	cellular component
GO:0048009	insulin-like growth factor receptor signaling pathway	ISS	biological process
GO:0046777	protein autophosphorylation	IMP	biological process
GO:0031642	negative regulation of myelination	ISS	biological process
GO:0005783	endoplasmic reticulum	TAS	cellular component
GO:0002063	chondrocyte development	ISS	biological process
GO:0030282	bone mineralization	ISS	biological process
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0004694	eukaryotic translation initiation factor 2alpha kinase activity	IMP	molecular function
GO:0004674	protein serine/threonine kinase activity	ISS	molecular function
GO:0032057	negative regulation of translational initiation in response to stress	TAS	biological process
GO:0032057	negative regulation of translational initiation in response to stress	TAS	biological process
GO:0017148	negative regulation of translation	TAS	biological process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process	ISS	biological process
GO:0005789	endoplasmic reticulum membrane	NAS	cellular component
GO:0005789	endoplasmic reticulum membrane	ISS	cellular component
GO:0005783	endoplasmic reticulum	ISS	cellular component
GO:0001503	ossification	IMP	biological process
GO:0001501	skeletal system development	ISS	biological process

KEGG pathways

Pathway id	Pathway name
hsa05168	Herpes simplex virus 1 infection
hsa05010	Alzheimer disease
hsa05012	Parkinson disease
hsa04141	Protein processing in endoplasmic reticulum
hsa04140	Autophagy - animal
hsa04932	Non-alcoholic fatty liver disease
hsa05160	Hepatitis C
hsa04210	Apoptosis
hsa05162	Measles
hsa04137	Mitophagy - animal

Diseases

Associated diseases	References
Permanent neonatal diabetes mellitus	KEGG:H00512
Wolcott-Rallison syndrome	KEGG:H00766
Permanent neonatal diabetes mellitus	KEGG:H00512
Wolcott-Rallison syndrome	KEGG:H00766
Wolcott-Rallison syndrome	PMID:10932183
type 1 diabetes mellitus	PMID:15483661
Cryptorchidism	MIK: 28606200

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq